Oligonucleotides, such as aptamers and antisense oligonucleotides have been used therapeutically. Oligonucleotides comprising a variety of chemical modifications and motifs have been described. In certain instances, such oligonucleotides are useful as research tools, diagnostic reagents, and as therapeutic agents. Certain antisense oligonucleotides comprising at least a region of DNA-like nucleosides have been shown to reduce protein expression. Certain such antisense oligonucleotides act at least partially through RNase H. Certain RNA-like antisense oligonucleotides are known to inhibit protein expression in cells. Such RNA-like oligonucleotides function, at least in part, through the RNA-inducing silencing complex (RISC). Antisense oligonucleotides may be single-stranded or double-stranded. Antisense oligonucleotides have also been shown to alter processing of pre-mRNA and to modulate non-coding RNA molecules. In certain instances antisense oligonucleotides have been shown to modulate protein expression by binding to a target messenger RNA (mRNA) encoding the protein. In certain instances, such binding of an antisense oligonucleotides to its target mRNA results in cleavage of the mRNA. Antisense oligonucleotides that modulate processing of a pre-mRNA have also been reported. Such antisense oligonucleotides alter splicing, interfere with polyadenlyation or prevent formation of the 5′-cap of a pre-mRNA.
Therapeutic oligonucleotides may be administered to an animal. In certain instances it is desired to detect or quantify the amount of therapeutic oligonucleotides in a biological sample from an animal to which a compound has been administered. Certain assays for such purposes have been reported. See for example U.S. Pat. No. 8,163,477. The present disclosure describes compounds and methods that have improved sensitivity, ease of use, and/or reduced cost compared to previously described assays.